This proposal, Clinical and Molecular Studies of Malignant Brain Tumors, builds upon my decade-long experience conducting highly productive patient-oriented research and successful mentoring of 26 neuro-oncology fellows at the Massachusetts General Hospital Cancer Center. The focus of the research strategy proposed in this application is to develop improved diagnostic and therapeutic approaches for malignant brain tumors. The protected time afforded to me during the first 5 years of this K24 award enabled me to complete multiple patient-oriented research projects, publish more than 95 papers, successfully compete for 3 peer-reviewed NIH and 2 foundation research grants as principal investigator, and mentor 11 current and past fellows and junior faculty members. Renewal of the award will enable me to expand my mentoring role to other oncology-related disciplines and to conduct patient-oriented research projects across new areas of neuro-oncology including brain metastases. Resources that will enable this expansion and assure success of a second 5-year period of funding include a neuro-oncology patient volume base that has doubled over the last 5 years, clinical trial accrual that has quadrupled over the last 5 years and a growing fellow and junior faculty group of investigators that provides an outstanding pool of potential mentees. In light of the expanding clinical volume it is imperative that I retain the ability to protect my time for patient-oriented research and mentoring. The expansion of my patient-oriented research and mentoring to other oncology-related disciplines will also enable me to secure additional peer-reviewed grant funding in new areas not currently represented in my active grant portfolio, which will further expand opportunities for future mentees. The award will enable me to further enhance my career as a patient-oriented researcher as well as my ability to mentor young investigators from neuro-oncology, medical oncology, neuroradiology/cancer imaging, transplant oncology and related disciplines.